System and method for selectively extracting individual vials from an array of vials within a rack

ABSTRACT

An automated storage system for storing large quantities of samples in trays includes a storage compartment, a tray shuttle compartment abutting the storage compartment on one side and a plurality of independent modules on the other side. The modules perform processing of samples that are retrieved from the storage compartment by a tray shuttle, including extraction of selected samples from retrieved source trays and transfer of the selected samples into a separate, destination tray that can be further processed or removed from the system for use. The independent operation of the modules permits handling and processing to be performed simultaneously by different modules while the tray shuttle accesses additional samples within the storage compartment. In one embodiment, a vertical carousel is used to vertically align a desired tray with the tray shuttle, while the tray shuttle operates within a horizontal plane.

RELATED APPLICATIONS

This application claims the benefit of the priority of U.S. ProvisionalApplications No. 60/761,736, filed Jan. 23, 2006, No. 60/799,706, filedMay 11, 2006, No. 60/808,470, filed May 24, 2006, and No. 60/820,338,filed Jul. 25, 2006, each of which is incorporated herein by referencein its entirety.

FIELD OF THE INVENTION

The present invention relates for systems for handling and storingbiological or chemical samples, and more specifically to an automatedsystem for storage, retrieval and management of large numbers of samplesretained in sealed arrays of storage containers.

BACKGROUND OF THE INVENTION

Many scientific and medical organizations, including industrialconcerns, regulatory agencies, research laboratories, and academicinstitutions, have the need for secure storage of very large numbers,e.g., a few thousand up to multiple millions, of samples and specimens.Such fields include pharmaceutical, biotechnology, laboratorydiagnostics, genomics, biospecimen, forensic, agrichemical and specialtychemical. Depending on the application, the sample sizes can vary fromtens of microliters to several drams, which are stored in small, sealedplastic tubes or vials. These containers are retained in a rack thatallows individual samples to be inserted or removed without removing anentire rack, or the tray the holds one or more racks. To extend theuseful lifetime of the samples, they are stored in a controlledenvironment of low temperature (typically −20° to −80° C. or lower), lowhumidity, and inert gas (nitrogen), and are subjected to as littleenvironmental variation as possible. In order to handle very largenumbers of samples in the most efficient manner, a number ofconsiderations must be made to enhance the system's flexibility andadaptability for different applications with the smallest possiblefootprint to minimize the use of valuable laboratory space.

An overview of currently available compound storage systems andtechnologies is provided by Dr. John Comley in his article entitled“Compound Management in pursuit of sample integrity”, published in DrugDiscovery World, Spring 2005, pp. 59-78, which is incorporated herein byreference.

Tracking of the samples is essential, and the sample containers, racksand trays are usually labeled with a bar code or other machine-readableidentifier. The identity and location of each sample is stored in asystem memory that maintains records for all samples in the storagesystem so that individual samples or subsets of samples can beidentified and rapidly retrieved from storage. Ideally, the retrievalprocess should occur without unnecessarily exposing samples to thawingor moisture, which means that the system must be capable of selectingindividual samples from one or more racks in the storage compartmentwhile minimizing exposure of other samples in the storage compartment,or in the same trays, to an environmental change. It is also importantthat the system be reliable so that it can be serviced without riskingexposure of the samples to undesirable conditions.

To prevent evaporation of the sample or exposure to contaminants duringstorage, the containers are usually covered with a cap or membranestretched across the open end of the container. In order to dealefficiently with the large numbers of containers in a tray, systems arecommercially available to simultaneously seal all containers within thetray with a sheet of material, such as foil or laminated polymer, thatis heat sealed or otherwise adhered to the top edges of all of thecontainers. These seals are pierceable or peelable to permit access tothe sample. After the containers are sealed, the excess seal materialbetween the containers is cut to separate the individual containers forsubsequent retrieval without requiring the entire tray of containers tobe thawed. After die cutting of the seals, the tray of containers isplaced in storage. The die cutting operation requires a separatehandling step, and usually, an additional piece of equipment withcomplex tooling that is specifically designed for a certain size andshape of tube, thus limiting the type of containers that can be used, orrequiring that multiple die cutting tools be available.

In certain applications, the samples are preferably stored at ultra-lowtemperatures (−80° C. or lower), however, this cold environment can behazardous to the electro-mechanical devices that are necessary foroperation of an automated system. Lubricants are less effective at suchlow temperatures, making the robotics less reliable. Maintenance ofrobotics in the sample storage area is particularly a problem becausethe storage environment must be thawed and opened, subjecting thesamples to condensation and possible thawing. Some commercial systemsisolate the robotics in a somewhat warmer compartment (−20° C.), passingthe samples between the two compartments. In such systems, an insulatingwall must be created between the two compartments to maintain thetemperatures in each compartment.

In existing systems, the sample storage areas have removable doors thatare opened to obtain access to the trays. In others, the trays (orstacks of trays), have a block of insulating material at one end so thatall trays together combine to form an insulated wall. When a tray isremoved, the insulating material associated with that tray is alsoremoved and must be replaced with a dummy block to maintain theintegrity of the insulating wall. This replacement process takes time,however, increasing the risk of temperature change in one or bothcompartments.

In large storage applications, the samples may need to be accessed bymultiple groups whose laboratory areas are in different locations withina facility, possibly even on different floors of a multi-story building.Access for loading and unloading sample containers in existing compoundstorage systems is located at a single location at the base of thestorage unit. This often results in transporting large numbers ofsamples on carts and potentially exposing them to undesirableconditions. Further, with all groups needing to access their samplesfrom a single station, time will be lost waiting for another user tofinish their sample storage or retrieval operation.

The present invention is directed to storage systems that address theforegoing concerns to provide the flexibility and ease of use of largevolume sample storage system.

BRIEF SUMMARY OF THE INVENTION

An automated storage system for storing large quantities of samples intrays includes a refrigerated storage compartment, a tray shuttlecompartment abutting the storage compartment on one side and a pluralityof independent modules on the other side. The modules perform processingof samples that are retrieved from the storage compartment by a trayshuttle, including extraction of selected samples from retrieved sourcetrays and transfer of the selected samples into a separate, destinationtray that can be further processed or removed from the system for use.The independent operation of the modules permits handling and processingto be performed simultaneously by different modules while the trayshuttle accesses additional samples within the storage compartment.

In a first exemplary embodiment, the automated sample storage andmanagement system of the present invention employs a vertical storagecarousel for the refrigerated storage compartment. Trays containing oneor more arrays of individual, removable sample containers fit into aplurality of slots located in carriers that rotate around the carousel.The slots are configured to permit sufficient clearance betweenvertically adjacent trays to accept a variety of different size samplecontainers or well plates. The vertical carousel reduces the footprintof the system and greatly improves reliability since the carouseloperation requires only a single motor that provides forward or reverserotation to position the desired tray, or tray slot, in alignment with ahorizontal tray loader/unloader mechanism, or “shuttle.

The vertical carousal storage mechanism combined with the horizontaltray shuttle allows retrieval times to be minimized by organizing thesequence of desired samples according to their locations in thecarousal. As one sample is retrieved, the next one on the list can bepre-positioned for retrieval by rotating the carousel to move the nexttray to the level of the tray shuttle. Other systems have fixedlocations for the samples. They can retrieve trays quickly when therequested samples are located near each other, but become substantiallyslower when retrieving samples stored at the most distant locations ofthe storage area.

The vertical carousel minimizes the mechanics necessary to interfacewith the tray shuttle that moves trays between the storage compartmentand one or more modules used for processing or inspection of thesamples. Because the vertical carousal moves vertically, a singlehorizontal axis is capable of providing access to every carrier and trayon the carousel. The tray shuttle is a conveyor on the horizontal axisthat is able to retrieve any tray across the entire width of thecarousel. The only component of the tray shuttle that extends into thestorage space is the tray hook. This rotating hook/lever device is ableto pull or push a tray to insert it into or remove it from a slot on thecarousel, to position the tray on the conveyor and to move it to anylocation where an operation is to be performed.

One or more modules are located on the front of the tray conveyor, onthe opposite side from the storage compartment. Each module is capableof receiving one or more trays from the tray conveyor and performingsome operation on the trays, such as modifying the contents of aparticular tray, selecting, or “cherry picking”, specific samples from atray and placing them in another tray, defrosting a tray for use,removal of the samples for use, or inspection of the samples. Themodules can be insulated and have a controlled atmosphere, includingbeing cooled to the same temperature as the tray conveyor and/or filledwith a gas to create an inert atmosphere. Because the tray conveyor andmodules are external to the storage compartment, they can be removed orserviced without disrupting the frozen environment of the storedsamples.

The modules may include liquid handling devices that can receive adefrosted tray, and at room temperature, preferably in an inertatmosphere, de-cap the containers, and aspirate and dispense a portionof the sample without removing the sample container from the system.

A significant benefit of the discrete modules is that it is practical tofill the storage compartment with an inert gas such as nitrogen, whichreduces concerns about contamination due to water or oxygen. Since thereis no need for human access to the storage area, the use of nitrogendoes not present a health hazard to those using the system.

The modular design also allows the system to be accessed at differentelevations along the height of the vertical carousel in addition to orother than the base of the system. This feature is useful where thestorage compartment is tall enough to span multiple levels of alaboratory facility. The nature of the carousal allows sample carriersto be positioned at any level. By providing a tray shuttle, module(s)and system control station on a second, third, or other floor, differentlaboratories can have localized access to a common storage compartment.Software in the system controller will prioritize requests for access insituations where requests are submitted at or near the same time fromdifferent laboratories.

In occasions where space is available in a basement, but where accesswould be inconvenient or undesirable, the system can be configured tohave access points only on the first and/or second floors with no accesspoint in the basement. This can add considerable storage capacitywithout taking up valuable laboratory floor space.

Each of the modules is capable of independent operation, allowingmultiple operations to be performed in parallel, and at least some ofthe modules include the ability to handle multiple trays at one time.This allows removal or replacement of trays in a module without the needto halt the operation of that module. For a selector, or“cherry-picking”, module, this means that the mechanism can runcontinuously. Two source tray locations are provided so that while themechanism is picking from one tray, the other can be replaced. Thesingle destination tray is replaced as it is filled. This techniqueallows the picking rate to be considerably faster than existing methodsbecause there is no down-time for the picking mechanism. The inventivedesign also improves reliability.

The selector module includes a pusher mechanism, which lifts the samplecontainers up and out of the tray, and a pick head, which has one ormore cavities for receiving the containers that are lifted by the pushermechanism. The pusher mechanism moves independently from the moveablepick head, allowing the pick head to receive multiple tubes fromdifferent locations of a tray. The pick head is then moved to adestination over destination tray and the ejector mechanism is actuated,placing all tubes in one motion.

The selector module can be configured to perform the function of diecutting, thus eliminating the need for an additional step, andadditional instrumentation, for separating containers within a rack thathave been sealed with a sheet of foil or polymer. In this embodiment,one or more cavities in the pick head have a sharp edge that is capableof cutting the seal around the perimeter of the sample container when itis pushed upward by the pusher mechanism. This allows the tubes to bestored with the seal intact until needed. Typically only a few samplesare needed at a time, so the seal is cut only around the containers ofthe samples that are desired when they are prepared for selection.

In an alternate embodiment of the storage compartment that isparticularly suitable for ultra cold storage, the vertical carousel isreplaced by stationary racks and a gantry-type tray shuttle, capable ofvertical and horizontal movement, which is housed within a warmer (˜−20°C.) compartment. The storage compartment is separated from the trayshuttle/gantry compartment by stacks of foam bricks that are arranged tocreate a robotically friendly insulating wall in front of the storagetrays. The blocks are arranged in stacks and held in place by gravity.Guide rails on either side of the stacks constrain the blocks againstlateral movement while allowing them to slide up and down freely. Toaccess a particular tray, the robotic loader/unloader moves to a blockin front of the desired tray, extends a pin or plate into acorresponding recess in the block, then lifts all of the blocks abovethat point. The tray of interest is extracted and the blocks are loweredto the original position. The blocks can be of any size but it ispreferable to keep them relatively small to minimize size of the gapneeded to access the desired tray position and, thus, minimize anytemperature change that might occur when the gap is temporarily openedin the wall. The inventive approach allows the opening to be immediatelyclosed after the tray is extracted, without the delays experienced withprior art systems that require a substitute tray to be retrieved to plugthe hole left by the extracted tray.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be more clearly understood from the followingdetailed description of the preferred embodiments of the invention andfrom the attached drawings, in which:

FIG. 1 is a diagrammatic cross-sectional side view of a first embodimentof the system showing the storage unit, shuttle and external modules;

FIG. 2 is a diagrammatic cross-sectional view taken along line 2-2 ofFIG. 1, showing the storage unit, tray shuttle mechanism, and exemplaryexternal modules.

FIG. 3 a is a diagrammatic perspective view of the first embodiment withthe storage unit housing removed; FIG. 3 b is a diagrammatic perspectiveview with the housing partially cut away to show elements of thecarousel mechanism; and FIG. 3 c is a detail view of versatile trayslots that permit storage of different size sample containers.

FIG. 4 is a diagrammatic top view of a second embodiment of the systemwith an insulating wall separating the storage compartment from the trayshuttle.

FIG. 5 a is a diagrammatic front view and FIG. 5 b is a perspective viewwith the housing partially cut away, both showing the tray shuttle andinsulating wall according to the second embodiment.

FIGS. 6 a-6 c are diagrammatic side views of the second embodimentshowing the steps for accessing and removing a tray from the storagecompartment by lifting the insulating.

FIGS. 7 a and 7 b are diagrammatic side and end views, respectively, ofthe tray shuttle.

FIGS. 8 a-8 n are a series of diagrams showing the tray hook sequencethrough which trays are retrieved from the storage compartment anddelivered to a module at the front of the system in preparation forcherry picking of specific sample containers.

FIGS. 9 a and 9 b are diagrammatic views (front and top) of the tubepicking function.

FIGS. 10 a-10 c are a front, side and perspective views, respectively,of a sample selector mechanism; FIG. 10 d is a top view of a fixture foruse with the sample selector for cutting seals around containers.

FIG. 11 a is a diagrammatic side view of a multi-story system withflexible access modules; FIG. 11 b is a perspective view of themulti-story system with the housing removed to show the verticalcarousel.

FIG. 12 is a diagrammatic view of an alternative embodiment of a sampleselector.

FIGS. 13 a and 13 b are diagrammatic views of the sample selector ofFIG. 12 before and after die cutting of a sealing sheet.

FIG. 14 is a block diagram of software and firmware elements of thecontrollers of the storage system.

FIGS. 15 a-d are diagrammatic top views of a series of reading steps toallow a fixed bar code reader to view the right, right rear, front, andleft rear sides of a sample vial, respectively.

FIG. 16 is a diagrammatic top view of two storage systems bridgetogether using a bridge module.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of the detailed description of the preferred embodiments,the following definitions are used:

A “sample” is used to describe a material (compound, biologicalspecimen, or other substance) that is or can be stored in a storagesystem, as well as a tube, vial and similar container which is thelowest unit of storage for retaining the stored material.

An “array” includes plates and racks that organize samples in a fixedarrangements. Racks hold removable sample containers while plates havenon-removable wells. Such racks are generally configured as an array ofvertical, open ended sleeves or slots, permitting access to theremovable containers retained within the slots.

A “tray” is a flat frame or container the holds multiple arrays.Generally, all trays within the storage system will be of the samelength and width, and the arrays within a given tray will all have thesame size sample. Exemplary trays have footprints to receive up to sixstandard SBS (Society for Biomolecular Screening) 8×12 racks and plates.The tray has a plurality of openings to permit containers to be accessedthrough the bottom of the tray as well as the top of the tray. Theopenings can have a large open center surrounded by a lip or ledge thatcatches the outer edges of an array plate to support the rack within thefootprint over the open area, permitting access to the underside of therack. Alternatively, the tray can have an array of smaller openingsthrough an otherwise continuous bottom surface, with each openingcorresponding to the position of a sample container, so that eachcontainer can be accessed through the opening.

Each sample, array and tray should be individually identified with a barcode or similar machine-readable indicator to permit tracking of eachsample, and the arrays and trays will generally have an orientationindicator, such as a notched corner, to facilitate handling and trackingof the samples.

A first exemplary embodiment of the automated sample storage andmanagement system of the present invention is illustrated in FIGS. 1-3.The basic components of the system 100 include storage compartmenthousing 102, storage compartment 110, vertical carousel track 120, traycarriers 121-124, tray shuttle compartment 140, tray shuttle 150,modules 160, 162, 164 and 166, and control station 170.

The vertical carousel mechanism, which is commercially available fromRemstar International, Inc. (Westbrook, Mass.), operates much like aFerris wheel, and is capable of clockwise or counter-clockwise rotationwhile maintaining each tray carrier in an upright position. FIG. 3 billustrates primary components of the carousel including verticalcarousel track 120, drive chain 125, upper drive gear 126, lower drivegear 127, transmission chain 128, transmission 129, and drive motor 130.As is known in the art, carrier guides 132, which are pivotably attachedto the sides of the carriers and pivotably linked to drive chain 125,have guide arms that slide within carousel track 120 to keep thecarriers upright throughout their travel.

Access to all trays in storage compartment 110 is obtained by activatingthe carousel to move the carrier 124 containing the desired tray, rackand sample into alignment with tray shuttle 150, which provideshorizontal movement along plane 152 that extends perpendicular to, andacross the front of, storage compartment 110 to permit access to everytray in carrier 124. The carousel controller is capable of haltingrotation in either direction with sufficient precision to horizontallyalign not only carrier 124, but each individual tray with the shuttle150. Shuttle 150, which is described in more detail below, also provideshorizontal movement toward and away from storage compartment 110 toallow trays to be pushed into or pulled from slots in carrier 124.

Each carrier 121-124 in the carousel is a four-sided shelf, with panelson the bottom, back and two sides, with multiple vertical partitions 322(shown in FIG. 3 a) to define a plurality of tray supports. (Note thatthe partitions 322 are shown only in carrier 122 for ease ofillustration, but each carrier will have multiple partitions, with thenumber of partitions depending on the tray widths and the widths of thecarriers.) Each vertical partition 322 has a plurality of tray supportslots (inwardly extending channels or ledges) separated by a widthcorresponding to the widths of the trays, so that the trays aresupported parallel to the bottom of the carrier. The slots areconfigured to permit sufficient clearance between vertically adjacenttrays to accommodate a variety of different size (height) racks andsamples. The versatile slot configuration is achieved by utilizing astandardized tray thickness for all types of arrays (racks and plates),regardless of the height of the container. The vertical partitions areformed with uniformly spaced horizontal ribs or rails extending theentire height of the partition 322, as illustrated in FIG. 3 c. Thedimensions of the tray slots 324 are such that the standard thicknesstrays 326 can be easily slid into and out of the appropriate slots toprovide sufficient clearance between the various size racks 328, 329,330 that can be retained on the trays 326.

The independent vertical and horizontal motion of the carousel and thetray shuttle permit more rapid access of samples that may be distributedthroughout the storage compartment. Retrieval times can be minimized byactivating the carousel while the shuttle is transporting a tray to aprocessing module, so that once the shuttle has transferred theretrieved tray to the module, the next carrier and tray will already behorizontally aligned with the shuttle so that the shuttle canimmediately move to the correct horizontal position to pull the nexttray.

Also part of the storage system, but not described or illustratedherein, are the refrigeration equipment and temperature control andmonitoring instrumentation. Such components are well known in the artand selection of appropriate components will be readily apparent tothose in the field.

One or more modules 160, 162, and 164 are located on the front of trayshuttle 150, on the opposite side from storage compartment 110. Eachmodule is capable of receiving one or more trays from the tray shuttleand performing some operation on the trays, such as modifying thecontents of a particular tray, cherry picking specific samples from atray and placing them in another tray, defrosting a tray for prior toremoval of the samples for use, inspection of the samples, or interfacewith and transfer samples to another storage system or materialprocessing station. This modular configuration allows the system user tocustomize the system to their own specific needs. For example, multiplecherry picker modules may be provided, with one module for selectingvials and another for selecting tubes. In an exemplary combination,module 160 is a vial selector, module 162 a tube selector and module 164an input/output-defroster. Other combinations of cherry picker modulescan include vial selectors for different size vials, or plate selectorswhich can remove specified plates from source trays and combine themwith other selected plates in a destination tray. The modules can beinsulated and have a controlled atmosphere, including being cooled tothe same temperature as the tray shuttle compartment 140 and/or filledwith a gas to create an inert atmosphere.

I/O-defroster module 164 is preferably supplied with well-stirred,heated air to maintain the maximum heated air temperature and overallcabinet temperature within a tightly regulated range. This enables rapidthawing without risk of hot spots that can overheat some samples. Module164 includes an access door 167 for removing trays from, and replacingtrays into, the module. A bar code reader 165 or other tracking devicewithin module 164 automatically reads and records the identities ofevery tray, rack and, if possible, sample container, that passes throughthe module and forwards these identities to system controller 170.System controller 170 will track trays removed from the system bychecking them out and checking them back in when they are inserted backinto module 164 and reloaded by the tray shuttle to ensure that thelocation of every sample, rack and tray is known at all times and toprevent inadvertent placement of a tray in an incorrect position in thestorage compartment when the samples are returned to storage.

While the I/O module 164 is capable of reading and recording the barcodes on trays, and racks, it can be difficult to read a bar code thatis affixed to a round bottle or vial since the container can rotate,directing the bar code away from a optical reader in fixed position.Conventional automation techniques will rotate the bottle by some meansso that the barcode will at some point pass in front of a fixed reader.Rotating devices add expense and are generally slow.

Vial picking module 160 includes an assembly for rapidly reading barcodes on vials without rotating the vial using a combination of aconventional fixed position reader and mirrors that are positioned topermit reading of the entire surface of the vial. In the case where thevial is already being moved by a robot, no additional mechanics may berequired.

Vial picking module includes a vial pick head with an automatedclaw-like mechanism that grasps only top of the vial, so that theportion of the vial bearing the bar code extends down from the pickhead. Such mechanisms are generally known in the art. FIGS. 15 a-dillustrate how three mirrors 351-353 can be attached to move along withthe vial pick head to reflect reading beam 370 to view different sidesof vial 360, allowing a fixed position bar code reader 362 to used. Beam370 is projected continuously forward. As the pick head, holding vial360, with attached mirrors 351-353 is translated left to right (asillustrated), the first position, shown in FIG. 15 a, aligns mirror 353with beam 370, allowing the right side of vial 360 to be read. In FIG.15 b, pick head continues is translation, placing mirror 352 intoposition to reflect beam 370, allowing the right rear side of the vialto be viewed by fixed reader 362. FIG. 15 c illustrates the pick headmoved so that beam 370 directly impinges upon the front of vial 360.FIG. 15 d shows the pick head in a position so that beam 370 isreflected by mirror 351 to view the left rear side of the vial. Thesefour different positions permit all sides of the vial to be viewed withsmall amounts of overlap such that at least one of the positions willproduce a signal corresponding to the vial's ID. Since the only movingpart is the pick head and its translation mechanism, if the reader hasnot detected a bar code after a single pass, the pick head can bereversed to a starting position, then activated to repeat its path pastthe reader.

The lack of moving parts, other than the single axis translator,provides for a robust reading system. Different configurations of mirrormay be also used. For example, two flat mirrors may be used to view theentire area but with no overlap, or one shaped mirror could be used. Themirrors can be positioned at some distance from the vial to providesufficient clearance for clamping mechanisms or other moving elements.In an alternate configuration, the reader can be moved (or rotated)relative to the vial and mirror assembly, which is stationary.

Yet another possible module for use with the inventive system is abridge module, which is illustrated in FIG. 16. As shown, bridge module169 is attached to the front of tray shuttle compartment 140 a at theright end of the row of modules 160, 162, 164 of a first storage system100 a. Bridge module 169 extends beyond the right end of system 100 aand attaches to the front side of tray shuttle compartment 140 b ofsecond storage system 100 b. This inventive design permits a system userto expand their storage capacity (double, triple or more) withoutdisturbing an existing storage system. Current commercial systemsrequire the storage compartment to be compromised if the system ownerwishes to expand the capacity of an existing system rather than purchasea new, larger system. This permits the system user to purchase the moreeconomical system for its currently needs and expand at a later date asneeded by purchasing one or more additional systems. The interfacebetween the two bridged storage systems permits rapid access to allsamples within all systems, allowing samples to be selected from eithersystem to perform selection and transfer of samples into a commondestination tray. The second storage system 100 b can have its I/Omodule 172 as shown, or it can transfer a retrieved tray from trayshuttle 140 b through bridge module 169 to tray shuttle 140 a and to I/Omodule 164. Preferably, module 169 will include a bar code reader totrack trays, racks and samples that may be moved from one storage systemto the other.

An additional module, with a similar function to that of the bridgemodule can serve as an automation interface for transferring trays,racks and samples to separate material handling workstations withoutmanually removing the tray from the storage system to transport it foradditional processing or high-throughput screening. An exemplarycommercially-available workstation is the BioCel Series AutomationSystem (Velocity11, Menlo Park, Calif.). The interface module can bepositioned in a similar manner to bridge module 169, with theworkstation located slightly to the side of the storage system, or itcan be positioned so that the workstation is in front of the storagesystem, with the automation interface module sandwiched between thestorage system and the workstation.

Each module is releasably connected to the front side of tray shuttlecompartment 140 by way of a small opening that is sealed with a gasket161. The modular construction of the storage system permits modules tobe removed or serviced without disrupting the frozen environment of thestored samples. During servicing, or when modules are exchanged, theopening between the removed module and the tray shuttle compartment canbe sealed with a dummy plate.

The processing of samples typically occurs within an enclosure on theupper portion of each module. Below the processing enclosure of eachmodule is a cabinet that encloses the hardware components forcontrolling each module and the interfaces between the modules and thetray shuttle. The software/logical architecture 600 of the system isshown in FIG. 14. Each module has its own dedicated hardware controller642, 644, 646, and each of these controllers is driven by a hardwarecontrol PC 630 which runs selector manager 632 and tray manager softwarefor controlling cherry picking and tray transport by the tray shuttle,respectively. A console/server PC 602 includes software for systemmanagement 606, storage management 610 and communication with a database608 containing information about each sample that is or has been in thesystem. PC 602 also provides an optional connection to an enterprisesystem via a network switch as well as interfacing with a videocontroller 620 that operates a video camera (not shown) for visuallytracking operations in each of one or more modules. Each PC 602 and 630is powered by a UPS (uninterruptible power supply)(not shown) that isalso housed within the cabinets in the bottom of the modules.

Additional modules can include liquid handling devices that can receivea defrosted tray, and at room temperature, preferably in an inertatmosphere, de-cap the containers, then aspirate and dispense a portionof the sample. The samples can then be re-capped without requiringremoval of the storage tray from the system. An exemplarycapper/de-capper system is disclosed in co-pending U.S. application Ser.No. 11/555,621, which is incorporated herein by reference.

The modular design permits the system to be accessed at differentelevations along the height of the vertical carousel in addition to orother than the base of the system, which is particularly advantageousfor multi-story storage systems. An exemplary set-up is illustrated inFIGS. 11 a and 11 b. Storage compartment 210 and vertical carousel guide220 span two stories, passing through the floor 280 that separates thetwo stories. Each floor has its own tray shuttle 250 a and 250 b, itsown controller 270 a, 270 b, and its own combination of processingmodules 260 a & b, 262 a & b and 264 a & b. By providing an opening on asecond, third, or other floor, different laboratories can have localizedaccess to a common storage compartment while utilizing processingmodules that are particularly suited to their needs. Software in thesystem controller will prioritize requests for access in situationswhere requests are submitted at or near the same time from differentlaboratories.

In situations where space is available in a basement for installation ofthe storage compartment, but where access would be inconvenient orundesirable, the system can be configured to have access points only onthe first and/or second floors with no access point in the basement.This can add considerable storage capacity without taking up valuablelaboratory floor space.

In multi-story systems, it may be desirable to incorporate a sensingdevice and a small amount of Z-axis positioning to accommodate shiftingor settling of the building structure and floors relative to the storagesystem so that the tray shuttle remains in proper alignment with thecarousel. These changes are typically small and occur over long periodsof time, so the throughput of the system is not affected. The modulesare coupled to the system in a way as to allow this small movementwithout disturbing the seal.

In an alternate embodiment (not shown), a multi-story or single storystorage system can be modified to provide access to a second laboratorylocated in a different room by attaching a tray shuttle compartment tothe back side of the storage compartment. The access points could be onthe same level or at different levels since the tray shuttle interactsonly with the immediately adjacent carrier. In this modification, thecarousel carriers would be open on the front and the back, allowingtrays to be removed from either side of the carriers. Both laboratorieswould have their own processing modules, which would provide more rapidaccess to samples.

Referring back to FIGS. 1-3, each of the modules 160, 162 and 164 iscapable of independent operation, allowing multiple operations ondifferent samples to be performed in parallel, and at least some of themodules include the ability to handle multiple trays at one time. Thisallows removal or replacement of trays in a module while the moduleoperates uninterrupted. For a selector, or “cherry-picking’, module asillustrated in FIGS. 9 a and 9 b, two source tray 930 positions areprovided on pick table 901 so that while the mechanism picker 902 isselecting samples from one tray 930, the other source tray can bereturned to storage and replaced with a different tray. The singledestination tray 932 is replaced as it is filled. This technique allowsthe picking rate to be considerably faster than existing methods becausethere is no down-time for the picking mechanism.

In an alternate embodiment of the storage compartment that isparticularly suitable for ultra cold storage, the vertical carousel isreplaced by stationary racks 520 and a gantry operated tray shuttle 452,capable of vertical and horizontal movement, that is housed within ahigher temperature (˜−20° C.) compartment. An exemplary gantry mechanismis disclosed in U.S. Pat. No. 6,663,334, which is incorporated herein byreference.

As illustrated in FIGS. 4-6, within storage system housing 402, storagecompartment 410 is separated from tray shuttle compartment 420 by a wall430 formed from stacks or columns of individual foam bricks or blocks(431-434 in FIG. 4 plus 531 a-f, 532 a-f, 533 a-f, and 534 a-f, in FIGS.5 a and b) that are arranged to create a robotically friendly insulatingwall 430. The blocks are arranged in stacks and held in place bygravity. Guide rails 540 on each side of the stacks constrain the blocksagainst lateral movement while allowing them to slide up and downfreely. As illustrated in FIG. 6 a, to access a specific tray, gantry552 moves horizontally along gantry rail 554 and moves robotic trayshuttle 452 vertically to align it with block 433 in front of thedesired tray 406. Pin drive mechanism 512, extends pin 506 into acorresponding recess 536 in block 433, the tray shuttle 452 moves upwardon gantry 552 to lift block 433 and all other blocks 533 a, 533 b abovethat point, as shown in FIG. 6 b. In the embodiment illustrated, pin 506is held at a fixed height above the tray support surface 458 of trayshuttle 452 by columns 456, so the system controller will be able todetermine exactly how much block 433 needs to be lifted to obtain accessto tray 406. In an alternative embodiment, a separate lift motor can beprovided on tray shuttle 452 to move horizontal drive mechanism 454vertically relative to tray support surface 458.

The tray of interest 406 is extracted by using tray hook 454 (shown inFIG. 4) to position the tray on tray support surface 458 of tray shuttle452. As illustrated in FIG. 6 c, tray 406 has been fully withdrawn, trayshuttle 452 is lowered to reposition blocks 433 and 533 a & b into theiroriginal position, and pin 506 is withdrawn, restoring the insulatingpartition between the storage compartment 410 and the tray shuttlecompartment 420. The blocks that make up the insulating wall can be ofany size but it is preferable to keep them relatively small to minimizesize of the gap created to access the desired tray position and, thus,minimize any temperature change that might occur when a gap istemporarily opened in the wall. The inventive approach allows theopening to be immediately closed after the tray is extracted, whichprovides a significant advantage over prior art systems that require asubstitute tray be retrieved and used to plug the hole left by theextracted tray.

FIGS. 7 a and 7 b illustrate the elements of tray shuttle 150, whichinclude shuttle frame 750, slide 714 which moves longitudinally alongframe 750 in response to activation of belt 710, drive wheel 712 andbelt guide 713, drive motor 715 which rotates drive wheel 712 clockwiseand counterclockwise to activate belt 710 to move slide 714 forward andbackward toward and away from the storage compartment. Slide guide rail738 extends upward from frame 750 to cooperate with slide guide channel736 on the bottom of slide 714 for repeatable motion. Extending from thetop of slide 714 is tray hook 730, which rotates around axis 734 whenactivated by tray hook motor 732, which is attached to the bottom ofslide 714. Tray hook 730 is configured to engage tray end hook 720 thatextends from each end of tray 706 (indicated by dashed lines) when movedinto contact with end hook 720.

Tray hook motor 732, when activated, rotates tray hook 730 to extendbeyond the end of tray shuttle 150 (as shown in FIGS. 8 a-8 n), so thatonly hook 730 reaches into the sample storage compartment. Tray hook 730can be used to either engage tray end hook 720 to enable the tray to bepulled onto tray supports 716, or can push against end hook 720 to slidethe tray off of tray supports 716 and away from tray shuttle 150.

FIGS. 8 a-8 n illustrate a sequence of operations performed by trayshuttle 150 for removing samples from storage compartment 110 andtransferring them to module 800. Starting with FIG. 8 a, tray 812 ispre-positioned within module 800, which in this example is a cherrypicker module. Tray 812 is a receiving tray into which selected sampleswill be placed during the picking operation. Tray hook 730 is located onthe right or front (module), side of tray shuttle 150 when the systemcontroller gives the command to retrieve tray 806, which has beenidentified as containing samples that are processed. If the storagecompartment employs the vertical carousel of the first embodiment, thecarousel will be rotated during this step to align tray shuttle 150 withthe carrier and tray to be retrieved. The tray shuttle 150 ishorizontally aligned with the desired tray 806. For the gantry-mountedtray shuttle of the second embodiment, the gantry will be activated tomove the tray shuttle 452 to the appropriate vertical and horizontalposition to begin retrieval.

In FIG. 8 b, tray hook 730 is moved to the left, or back (storagecompartment), side of shuttle 150 by activating drive motor 715 to moveslide 714 to the back. In FIG. 8 c, tray hook motor 732 is activated torotate tray hook 730 counterclockwise, causing the end of hook 730 toengage tray end hook 826 of tray 806.

Once the two hooks are engaged, drive motor 715 is activated to moveslide 714 toward the front of shuttle 150, pulling tray 806 out ofstorage compartment 110, as shown in FIG. 8 d. If needed at this point,tray shuttle 150 will move laterally along tray shuttle plane 752, organtry 552 will move tray shuttle 450 horizontally, to position the trayfor delivery to module 800. As illustrated, however, module 800 isdirectly in front of the location from which tray 806 is pulled.

In FIG. 8 e, tray hook 830 is rotated clockwise to disengage it fromtray end hook 826. Slide 714 is then activated to move it to the back oftray shuttle 150, as shown in FIG. 8 f. In FIG. 8 g, tray hook 730 isrotated clockwise again to engage end hook 836 of tray 806. Slide 714 isthen activated to move to the front of tray shuttle 150, pushing tray806 through an opening in the back of module 800, as shown in FIG. 8 h.Tray hook 730 is rotated counterclockwise to release end hook 836, shownin FIG. 8 i, after which tray shuttle 150 moves horizontally along trayshuttle plane 152 to position the shuttle in front of the next tray tobe retrieved, in this case tray 804, as shown in FIG. 8 j.

During the operation of tray shuttle 150 to complete the steps shown inFIGS. 8 g to 8 i, in the embodiment of FIGS. 1-3, the vertical carouselcan be activated to pre-position the next carrier at the tray shuttlelevel. Thus, tray 804 need not have been retained within the samecarrier as was tray 806. Nonetheless, because of the independentoperation of the vertical carousel and the tray shuttle, it is possibleto make the next tray available for retrieval immediately after the trayshuttle is freed up after delivery of the previous tray 806 to module800.

In FIG. 8 k, slide 714 is moved toward the back of tray shuttle 150,positioning tray hook 730 in front of tray 804. Tray hook motor 732 isactivated to rotate tray hook 730 counterclockwise to engage tray endhook 824, as shown in FIG. 81. Slide 714 is activated to pull tray 804onto tray shuttle 150, as shown in FIG. 8 m, then tray shuttle 150 ismoved along shuttle plane 152 to position tray 804 for transfer tomodule 800, as shown in FIG. 8 n. The steps illustrated in FIGS. 8 g and8 h will then be followed to move tray 804 into module 800.

Once the desired samples have been removed from trays 804 and 806, thetray shuttle will operate in a reverse sequence to return the trays totheir previous position. Additional trays can be retrieved andtransferred to module 800 to obtain all of the desired samples fortransfer into tray 812.

After tray 812 is filled with the desired samples, tray shuttle 150 canbe used to return the samples to storage or to transfer the tray to adifferent module. Typically, the second module will perform a processingoperation, such as de-frosting the samples in a controlled, e.g., inertand/or temperature ramped, environment to minimize condensation beforethe samples are removed from the system for use. The same module can beused for introducing samples into the colder temperatures of the storagecompartment, subjecting them to an inert atmosphere before they areplaced in storage. Other modules can include video or analyticalinstrumentation for inspection and/or testing of the samples.

FIGS. 9 a and 9 b illustrate the picker mechanism 902 that is utilizedin a cherry picker module 900 for tubes. As previously mentioned, thepicker module 900 has two source tray positions 920, 921 and onedestination tray position 950, which hold multiple sample racks 922 and952, respectively. The trays are supported on a stationary surface, or“pick table” 901, while the picker mechanism moves within an x-y planeto access different locations on the trays to perform the desiredtransfer operations. While samples are being extracted from one sourcetray position, a different source tray can be moved into the othersource tray position, allowing for virtually continuous sampleselection.

Picker mechanism 902, which is mounted on a linear translator formovement along one axis 916 (the y-axis in FIG. 9 b), includes pick head904 and pusher mechanism 906. Pick head 904 translates along the otheraxis (x-axis in FIG. 9 b) along rail 910, while the positioning ofpusher mechanism 906 is controlled by screw drive 908.

Pusher mechanism 906 lifts the sample containers up and out of the racks922, pushing them into one or more cavities in pick head 904. The pushermechanism 906 moves independently from pick head 904, allowing the pickhead to receive multiple tubes from different locations of a tray. Oncethe cavity or cavities in the pick head are full, pick head 904 is movedto a destination over a rack 952 in destination tray 950, where anejector mechanism is actuated, placing all containers in one motion.

FIGS. 10 a-10 c illustrate the elements of the pick head 904 and pushermechanism 906.

Pick head 904 is mounted on rail 910 by way of mounting plate 948, withalso provides the frame for attachment of the pick head components. Pickhead bottom plate 931 extends perpendicular to mounting plate 948 andhas an opening through which the sample containers pass. Bottom plate931 will generally be located a short distance above the rack 922 fromwhich the samples are being picked. When the picker is also being usedto separate tubes that have been sealed with an adhesive sheet, asdescribed below, bottom plate 931 may actually contact the top surfaceof the rack 922. Just above bottom plate 931 are springs 961-963 whichare releasably attached to block 945 to extend downward. Each spring961-963 is formed from a resilient metal and has an inwardly extending atapered tooth that causes the spring to cam outward when a samplecontainer is pressed upward against the tooth. The inner surface of eachspring 961-963, the lower surface of block 945, and back wall 976 definecavity 960 within which sample containers can be retained during thepicking process. The size of the cavity, which is primarily defined bythe length of springs 961-963 between the upper edge of the taperedtooth and the bottom surface of block 945, should closely fit the sizeof the container in order to ensure proper operation. When differentlength containers are to be handled, the springs 961-963 are removed byunscrewing the spring screws and replaced with springs that have lengthscorresponding to the containers to be handled. The spring retains itsassociated container within cavity 960 until the container is ejected.

Sensor/ejector blades 952-954 slidably extend through slots in block 945so that when a container is pushed into cavity 960, the blade above thecontainer is pushed upward so that the upper end of the blade ispositioned for detection by one of a set of optical detectors 958 thatare mounted on a printed circuit board 933 above block 945. (PCB 933provided electrical connection to the picker controller (not shown).)Activation of the optical sensor 958 produces a signal that tells thepicker controller that a container is retained within a given slot inthe pick head. As illustrated in FIG. 10 a, container 946 is retainedwithin cavity 960, thus pushing blade 954 upward where its upper end isdetected by optical sensor 958. Container 944 is in the process of beingpushed up against the tapered tooth of spring 962 by pusher rod 970. Thetop of container 944 will contact with the lower edge of blade 953 topush it upward where it, too, will be detected by the correspondingoptical sensor 958. In the exemplary embodiment, the pick head isconfigured for accepting three containers, as there are three springs961-963, three blades 952-954 and three optical sensors 958. Once alloptical sensors have detected the presence of a container in the cavity960, the picker controller directs the pick head to move to a positionof a destination rack 950 (in FIG. 9 b) into which the sample containersare to be placed. Once the pick head is in position over destinationrack 950, cam motor 934 is activated to rotate flywheel 958, causing camwheel 947 to apply a downward force against channel 938. Channel 938 isattached to the back side of pick head slide 935, causing slide 935 tomove downward along guide 936. Extending from the front side of slide935 is ejector bar 943, which has an ejector tab that extends through aslot in each of blades 952-954. As slide 935 moves downward, ejector barforces blades 952-954 downward against the tops of the containers incavity 960, ejecting them simultaneously from the pick head and into thedestination rack. Flywheel 958 can be weighted to provide additionalinertia upon activation to ensure that it follows its full cycle.

While the above explanation describes a pick head adapted for receivingthree containers, it will be readily apparent that more or fewercontainers can be handled by providing from onecavity-spring-blade-sensor combination to many such combinations as maybe practical for efficient operation.

Pusher mechanism 906 cooperates with pick head 904 by driving pusher rod970 upward, through the open bottoms of tray 920 and rack 922 to liftthe container up and push it upward against the toothed springs of thepick head. Pusher mechanism 906 is attached to translator 908 viamounting plate 968 to permit independent movement of the pusher and pickhead. Pusher rod is attached to pusher slide 937 which moves verticallyalong column 973, stabilized by pusher guide 974, both attached to base932. Vertical motion is initiated by a similar cam mechanism as thatdescribed above for the pick head ejector. Cam motor 940 rotatesflywheel 972, which moves cam wheel 964 within channel 966 to applyupward or downward force against the channel 966. Channel 966, which isattached to the back side of pusher slide 937, causes pusher rod 970 tomove up or down, depending on the direction of rotation of flywheel 972.As with the pick head, flywheel 972 can be weighted to ensure that itproduces sufficient inertia to complete its full cycle. Pusher rod 970can be replaced with different length rods as may be needed for handlingdifferent length containers.

Each of cam motor assemblies 934, 940 includes a magnetic positionsensor 941 or 939, respectively, which provides feedback on the positionof the corresponding flywheel 958 or 972 to ensure that the flywheel isrotated through its full cycle. Control electronics are located withinthe boxes attached to the ends of the motors.

Pick head 904 can be modified to perform the function of die cutting,thus eliminating the need for an additional step, and additionalinstrumentation, for separating containers within a rack that have beensealed with a single sheet of foil or polymer. In this embodiment, acutting plate 980 is affixed to the bottom of pick head bottom plate 931with cutting edge 982 aligned with the bottom of cavity 960. Cuttingplate 980 can be formed from aluminum or stainless steel. Edge 982 neednot be intentionally sharpened since the normal process of machining theplate to form the opening by cutting or drilling produces a sharp enoughedge to cut the seal around the perimeter of the sample container whenit is pushed upward by the pusher mechanism. This allows the tubes to bestored with the seal intact until needed. Typically only a few samplesare needed at a time, so the seal is cut only around the containers ofthe samples that are desired when they are prepared for selection.

FIG. 12 illustrates an alternative embodiment of the cherry picker wherethe pick head carries a single sample at a time. In this case, the pickhead 988 and pusher 985 are supported on the same frame and do not moveindependently of each other. This configuration is particularly suitedfor handling racks that hold very small (50-100 microliter) tubes, whichare the type most commonly sealed with a sheet 990 of foil or polymer.Such racks may hold as many as 384 tubes. Since the ejector in the pickhead is only required to release one tube at a time, the ejectormechanism is a single pin 986 that is activated by a cam 996 that liftsup on lever 995 to compress bias spring 996 to apply downward forceagainst a tube within the pick head cavity.

As illustrated in FIGS. 13 a and 13 b, the cherry picker mechanism ofFIG. 12 is particularly well adapted for separating tubes that have beensealed with a sheet 990. When pusher 985 applies force against thebottom of the tube, it is pressed against the sharp edges 982 of thepick head, cutting the seal 990′ to separate the tube which is thenpushed up into the cavity, in contact with spring 993 and ejector pin986. When the cherry picker is moved to the destination tray, ejectorpin is activated to press downward on the tube to push it out of thecavity.

The sample storage systems described herein address many of theshortcomings of prior art systems to provide rapid access to samples inan environmentally controlled storage compartment with minimal impact onthe storage compartment environment. The flexible modules that can beinterchangeably and separably attached to the storage compartment arecapable of continuous operation when used in conjunction with a robotictray shuttle mechanism with a minimum number of electromechanicalcomponents that can be negatively impacted by the low temperaturestorage environment.

The cherry picker mechanism provides for rapid retrieval of selectedsamples without subjecting other samples in the same tray toenvironmental changes. Multiple cherry picker modules can be associatedwith a single storage compartment and tray shuttle so that differenttypes and sizes of sample containers can be stored, handled and managedwithin the same storage system.

It will be apparent to those skilled in the art that variousmodifications and variations may be made in the system and devices ofthe present invention without departing from the spirit and scope of theinvention. Thus, it is intended that the present invention encompass allsuch modifications and variations to the extent that they fall withinthe scope of the appended claims and their equivalents.

1.-28. (canceled)
 29. A system for selecting individual vials from anarray of vials disposed in one or more source trays and depositing theselected vials into a destination tray, wherein each of the source traysand destination tray has an open bottom, the system comprising: a picktable disposed in an x-y plane for supporting the one or more sourcetrays and destination tray; a pusher disposed below the one or moresource trays, the pusher comprising a push rod and a push rod motor forlifting the push rod upward through openings in the one or more sourcetrays and for lowering the push rod; a pick head disposed above the oneor more source trays, the pick head having a cavity for receiving theselected vial when the push rod is aligned with the cavity and the pushrod motor activated to lift the selected vial from the tray by pushingit upward into the cavity; and one or more translators for translatingthe pick head and the pusher within the x-y plane to access all vials inthe one or more source trays and all positions in the destination tray.30. The system of claim 29, wherein the cavity has a spring disposedtherein for releasably retaining the selected vial within the cavity.31. The system of claim 29, wherein the cavity is dimensioned forreceiving a plurality of vials and the pick head further comprises anejector for simultaneously ejecting the plurality of vials retainedwithin the cavity.
 32. The system of claim 31, wherein the pick headfurther comprises a plurality of sensors for detecting vials within thecavity.
 33. The system of claim 32, wherein the one or more translatorstranslates the pick head to the destination tray in response todetection of each of the plurality of vials within the cavity.
 34. Thesystem of claim 29, wherein the pick head and the pusher each has aseparate translator for independent translation within the x-y plane.35. The system of claim 29, wherein the pick head and pusher aretranslated together within the x-y plane.
 36. The system of claim 29,wherein the vial is retained within a rack sealed with a sheet seal andthe pick head further comprises a seal cutting edge near a lower edge ofthe cavity, wherein the pusher pushes the sample container against theseal cutting edge to cut the seal around the container before pushingthe container into the cavity.
 37. A method for selecting individualvials from an array of vials disposed in one or more source trays, themethod comprising: supporting the one or more source trays on a picktable within an x-y plane, wherein the one or more source trays have anopen bottom; translating a pusher disposed below the one or more sourcetrays to a position of a selected vial within the x-y plane; translatinga pick head disposed above the one or more source trays to the positionof the selected vial, the pick head having a cavity for receiving theselected vial when the pick head and the pusher are aligned; activatingthe pusher to pass through the open bottom of the source tray to liftthe selected vial from the source tray and push it upward into thecavity in the pick head; retaining the selected vial within the cavity;translating the pick head to a position within a destination tray; andejecting the selected vial into the position within the destinationtray.
 38. The method of claim 37, wherein the cavity is dimensioned forreceiving a plurality of vials and further comprising repeating thesteps of translating the pusher and translating the pick head to thepositions of a plurality of selected vials and activating the pusheruntil the plurality of vials is retained within the cavity.
 39. Themethod of claim 38, wherein the step of ejecting comprisessimultaneously ejected the plurality of vials into positions within thedestination tray.
 40. The method of claim 38, wherein the cavity has aplurality of sensors for detecting presence of vials within the cavity,the method further comprising detecting the plurality of vials withinthe cavity before translating the pick head to the position within thedestination tray.
 41. The method of claim 37, wherein the vial isretained within a rack sealed with a sheet seal and the pick headfurther comprises a seal cutting edge near a lower edge of the cavity,wherein the pusher pushes the sample container against the seal cuttingedge to cut the seal around the container before pushing the containerinto the cavity.